title: Pharmacodynamic and pharmacokinetic study of pegylated liposomal doxorubicin combination (CCOP) chemotherapy in patients with peripheral T-cell lymphomas.
abstract: OBJECTIVE
  To investigate the pharmacodynamic and pharmacokinetic parameters of pegylated liposomal doxorubicin (PLD) combined with cyclophosphamide, vincristine, and prednisolone in patients with peripheral T-cell lymphomas (PTCL).
  
  
  METHODS
  Seven chemonaive patients and four patients with relapsed peripheral T-cell lymphomas were treated with a CCOP regimen consisting of an intravenous administration of cyclophosphamide (750 mg/m(2)), vincristine (1.4 mg/m(2)), and PLD (30 mg/m(2)) on d 1, as well as an oral administration of prednisolone (60 mg/m(2)) on d 1-5. This regimen was repeated every 3 weeks for six cycles, and the clinical response and toxicity of the regimen were monitored. In addition, the plasma concentration of PLD at different time points was determined before and after treatment. The pharmacokinetics (PKs) software was used to estimate the pharmacokinetic parameters of PLD.
  
  
  RESULTS
  The 11 PTCL patients received 35 treatment cycles. Three of them achieved complete response (CR), two partial response (PR), four stable disease (SD), and two progressive disease (PD). The overall response rate (ORR) was 45.5%, and the CR rate was 27.3%. In the 7 chemonaive patients, three achieved CR, two PR, one SD, and one PD. The ORR was 71.4%, and CR rate was 42.9%. The median follow-up time was 15 months, but 6 out of 11 patients were dead at the time of data analysis. The 1-year overall survival rate was 45.5%, and the median progression-free survival (PFS) rate was 6.5 [95% confidence interval (95% CI) 3.17-19.02] with a survival rate of 11.5 months (95% CI 6.65-16.36). The main toxicity was myelosuppression. Oral mucositis and hand-foot syndrome seldom occurred. The PLD plasma concentration from nine patients ranged from 1.7036 to 9.2207 mg·L(-1) after administration of the CCOP regimen (0-168 h). The pharmacokinetic parameters AUC(0-∞), CL, t(1/2), and V(d) were 910.76 mg/L·h, 0.043 L·h(-1)·m(-2), 68.40 h, and 3.56 L/m(2), respectively.
  
  
  CONCLUSIONS
  The CCOP regimen was effective and well tolerated in patients with peripheral T-cell lymphomas. The results of the pharmacokinetic parameters showed that PLD had long retention time in blood circulation.
authors.affiliation: Department of Chemotherapy Center, Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Fan
authors.forename: Neng-ming
authors.initials: NM
authors.lastname: Lin
authors.forename: Lü-hong
authors.initials: LH
authors.lastname: Luo
authors.forename: Luo
authors.initials: L
authors.lastname: Fang
authors.forename: Zhi-yu
authors.initials: ZY
authors.lastname: Huang
authors.forename: Hai-feng
authors.initials: HF
authors.lastname: Yu
authors.forename: Feng-qin
authors.initials: FQ
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011241:Prednisone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D014750:Vincristine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone